Nitroxigenic Transmission

These flashcards cover key concepts and information about Nitric Oxide as a neurotransmitter, including its properties, signalling mechanisms, and implications in disease.

What are the main properties of Nitric Oxide as a neurotransmitter?

• Free radical ~ highly reactive

• Membrane permeant so doesnt need receptors to diffuse into target

• Perfectly suited for short range transmission

How is NOS synthesised?

L-arginine is oxidised to citrulline + NO

What criteria define a substance as a neurotransmitter?

• Synthesis on demand

• Storage in synaptic vesicles

• Release by exocytosis

• Actions at post-synaptic receptors

• Inactivation/uptake

Which enzyme synthesizes Nitric Oxide?

Nitric Oxide Synthase (NOS).

What is the role of soluble guanylyl cyclase in NO signalling?

sGC acts as a receptor for NO → cGMP levels increase → protein kinase cascade → depolarisation (lowering of intracellular Ca2+) → neuronal signal

How is NO involved in the regulation of vascular smooth muscle?

As a vasodilator, NO promotes relaxation of vascular smooth muscle through cGMP signaling.

What role does Calcium (Ca2+) play in the synthesis of NO?

Ca2+ is required for the activity of neuronal NOS (actions due to an influx of ions) but not for inducible NOS (iNOS).

How does NO signalling in the PNS lead to smooth muscle relaxation?

Synthesis of NO is triggered by an influx of Ca2+ ions

cGMP levels increase

There is co-transmission of ACh, NO and VIP (released simultaneously)

All pathways act together to promote smooth muscle relaxation and vasodilation in salivary glands

What are the implications of NO in the central nervous system (CNS)?

NO regulates excitability, firing, long-term potentiation and depression, and plays a role in learning and memory.

Excess NO may be neurotoxic

High densities in the cerebellum and accessory olfactory bulb

What are NANC neurones?

Non-adrenergic, Non-cholinergic

What neurotransmitters/peptides do co-transmission with NO?

• VIP - eye, salivary glands, cerebral arteries

• ACh - salivary glands

• ATP - rabbit portal vein

• Glutamate, GABA - cerebellum

How does Nitric Oxide exert its effects on overactivity?

It increases neurotransmitter outflow and plays a role in their basal release

How does NO contribute to neurotoxicity in stroke?

In a stroke, oxygen uptake increases, as overall oxygen level is lower.

NO + O2- → ONOO- (peroxynitrite - causes oxidative injury)

ROS production triggers the release of glutamate → neuronal Ca2+ overload → prolonged NO synthesis → neurotoxicity

What is the role of NO in Parkinson’s Disease?

Excess NO contributes to degeneration of dopaminergic neurones in the substantia nigra

Activated microglia → ↑ iNOS → ↑ NO